These projects are directed towards a greater understanding of the quaternary organization of plasma lipoproteins and of the function of the oligomeric species involved in the transport and metabolism of lipids in plasma. The apolipoprotein composition of plasma lipoproteins is viewed as the governing factor in directing lipoprotein metabolism. Specificity is believed to be related directly to apolipoprotein secondary, tertiary, and quaternary structure. A knowledge of the equilibrium constants and stoichiometry for the specific complexes formed in plasma by apolipo- proteins has allowed us to develop a framework for evaluating the role of apolipoproteins in controlling lipid metabolism. These studies have been extended recently to include lipoprotein lipase and hepatic lipase, two enzymes responsible for triglyceride hydrolysis. We have shown that both active and inactive forms of lipoprotein lipase exist in solution. The active form is the dimer and dissociation results in irreversible inactivation. The active species of hepatic lipase is also the dimer. Radiation inactivation studies demonstrate that the minimal functional unit required for active human and bovine lipoprotein lipase and human hepatic lipase is the dimer. Although lipoprotein lipase and hepatic lipase have many similar properties, they are clearly different enzymes. Three new peptide modifiers of lipase activity have been identified. One of these peptides activates phospholipid hydrolysis by hepatic lipase while inhibiting corresponding triglyceride hydrolysis.